Hydrochloric Acid → (R)-2-(4-Fluoro-3,5-dimethyl-phenylamino)-hexanoic acid

HRID 885501

Reaction equation

HRID 885501 reaction equation
[NH2:1][C@H:2]([CH2:6][CH2:7][CH2:8][CH3:9])[C:3]([OH:5])=[O:4].Br[C:11]1[CH:12]=[C:13]([CH3:19])[C:14]([F:18])=[C:15]([CH3:17])[CH:16]=1.C([O-])([O-])=O.[K+].[K+].Cl>C(OCC)(=O)C.O.[Cu]I.CC(N(C)C)=O>[F:18][C:14]1[C:15]([CH3:17])=[CH:16][C:11]([NH:1][C@H:2]([CH2:6][CH2:7][CH2:8][CH3:9])[C:3]([OH:5])=[O:4])=[CH:12][C:13]=1[CH3:19]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 456468Norleucine, D-(-)-HCID 27362985-Bromo-2-fluoro-1,3-dimethylbenzene

Product 1

HCID 69189506(R)-2-(4-Fluoro-3,5-dimethyl-phenylamino)-hexanoic acid

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

(R)-2-Amino-hexanoic acid (0.840 g, 6.4 mmol), 5-bromo-2-fluoro-1,3-dimethyl-benzene (1.292 g, 6.4 mmol), CuI (0.122 g, 0.64 mmol), and K2CO3 (1.326 g, 9.6 mmol) were weighed into a Schlenk flask. To this was added 8 mL of dimethylacetamide and the resulting mixture vacuum-pumped and nitrogen-filled alternatively three times. After heating to 90° C. with stirring for 39 h, the reaction mixture was cooled to room temperature, diluted with 20 mL of ethyl acetate and 10 mL of water, and then acidified with concentrated HCl to pH=3. The layers were separated and the aqueous layer extracted with ethyl acetate (20 mL×5). The organic layers were combined and dried over anhydrous Na2SO4. Removal of the solvent under reduced pressure gave the title product which was used directly in the next step with further purification. LC-MS: tR=8.5 min, m/z 254 (M+H)+.

Workup

  1. additionthe resulting mixture vacuum-pumped and nitrogen-filled alternatively three times
  2. temperaturethe reaction mixture was cooled to room temperature
  3. customThe layers were separated
  4. extractionthe aqueous layer extracted with ethyl acetate (20 mL×5)
  5. dry with materialdried over anhydrous Na2SO4
  6. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-fa77dd1252564d68b6b8a2dd1d36679e
Source dataset
uspto-grants-2012_08
Patent number
US08242174B2

Linked notes

Loading…